The Role of Primary Cilia in Mammary Gland Biology

初级纤毛在乳腺生物学中的作用

基本信息

批准号：
7862647
负责人：
KIMBERLY M MCDERMOTT
金额：
$ 24.9万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-15 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7862647
关键词：
Address Adenoviruses Adult Affect Age Alveolar Animals Antibodies Architecture Basement membrane Biology Carrier Proteins Cell surface Cells Centrosome Cilia Communication Control Animal Data Defect Detection Development Developmental Process Distant Duct (organ) structure Ductal Environment Epithelial Epithelial Cells Epithelium Etiology Event Extracellular Matrix Fatty acid glycerol esters Figs - dietary Flow Cytometry Functional disorder Genes Genetic Models Gland Hereditary Disease In Vitro Invaded Kinesin Label Lactation Lobular Mammary gland Measures Mediating Membrane Microtubules Milk Modeling Morphogenesis Mothers Motor Mus Mutant Strains Mice Mutation Myoepithelial Myoepithelial cell Nature Nurses Organ Organelles Organoids Pathology Pattern Phase Play Polycystic Kidney Diseases Positioning Attribute Pregnancy Process Production Proteins Puberty Recombinants Reporting Research Role Sensory Side Signal Transduction Site Smooth Muscle Actin Staining Method Sorting - Cell Movement Stromal Cells Structure Surface Testing Time Tissue Harvesting Tissues Transplantation Trees Tubulin Vagina Vertebrates Weight Wild Type Mouse Work base design functional loss gamma Tubulin in vivo insight interstitial malignant breast neoplasm mammary gland development mouse model mutant pregnant protein complex pup receptor-mediated signaling

项目摘要

The primary cilium is a membrane-enclosed organelle that projects from the surface of the cell and acts as the cell's antennae to communicate with its environment. The primary cillum senses signals from the environment and transduces receptor-mediated signaling events that control fundamental processes of developmental abnormalities and genetic diseases. I have demonstrated that the majority of primary cilia found in the murine and human mammary glands are expressed on the surface of myoepithelial cells. Nothing is known about the function of the cilium in the environment. Cilia projecting from the surface of myoepithelial ceils are Ideally positioned to play a sensory role to regulate stromal-epithelial as well as myoepithelial-luminal epithelial interactions. Communication between the microenvironment plays a critical role in the expansion and function of the mammary ductal tree during development, pregnancy, lactation and involution. I hypothesize that cilia mediate stromal-epithelial and myoepithelial-luminal epithelial communications to regulate mammary gland development, pregnancy and lactation. The specific aims described in this application are designed to characterize the pattem of expression of primary cilia and determine the function of primary cilia in normal mammary gland development, pregnancy, lactation and involution. I will analyze the mammary glands from murine models of ciliary dysfunction to determine whether ductal invasion, branching morphogenesis, tissue architecture, lobular-alveolar differentiation, lactation and involution are abrogated by loss of functional cilia. Preliminary data indicate that ductal invasion, branching morphogenesis, lobular-alveolar differentiation and lactation are decreased in the absence of functional cilia. Preliminary data also suggests that canonical Wnt signaling is increased and noncanonical Wnt signaling is decreased In the absence of functional cilia. These exciting results suggest that the primary cilium is involved in regulating Wnt signaling during mammary gland development. Given that cilia appear to control processes important in mammary gland development and breast cancer, such as ductal invasion, branching morphogenesis and differentiation, developing a better understanding of the mechanisms by which cilia function may provide important insight into the etiology and progression of breast cancer. I also believe studying primary cilia in the mammary gland will uncover ciliary functions that will contribute to a better understanding of the many genetic diseases caused by ciliary dysfunction.

原发性纤毛是一种膜封闭的细胞器，它是从细胞表面投射并作用的作为细胞的触角与环境进行通信。主要的cillum感应来自环境并传递受体介导的信号事件，以控制的基本过程发育异常和遗传疾病。我已经证明了大多数主要纤毛在鼠和人类乳腺中发现的腺体表面表达在肌上皮细胞的表面。关于纤毛在环境中的功能一无所知。纤毛从表面投射肌上皮天花板是理想的位置，可以发挥感官作用，以调节基质上皮和肌上皮上皮相互作用。微环境之间的沟通起着至关重要的作用在发育，妊娠，泌乳和互动。我假设纤毛介导基质上皮和肌上皮上皮传播以调节乳腺发育，妊娠和泌乳。本应用程序中描述的具体目的旨在表征原发性纤毛并确定原发性纤毛在正常乳腺发育，妊娠，妊娠中的功能哺乳和互动。我将分析从睫状功能障碍的鼠模型到确定导管入侵，分支形态发生，组织结构，小叶 - 肺泡通过功能性纤毛的丧失，消除了分化，泌乳和不合适。初步数据表明导管浸润，分支形态发生，小叶 - 肺泡分化和泌乳的减少缺乏功能性纤毛。初步数据还表明，规范的Wnt信号已增加，并且在没有功能性纤毛的情况下，非规范的Wnt信号传导降低。这些令人兴奋的结果表明原发性纤毛参与调节乳腺发育过程中的Wnt信号传导。鉴于纤毛似乎控制着对乳腺发育和乳房重要的过程癌症，例如导管侵袭，分支形态发生和分化，发展更好了解纤毛功能可以提供对病因和病因的重要见解的理解乳腺癌的进展。我还认为在乳腺中研究原发性纤毛会发现睫状将有助于更好地理解睫状体引起的许多遗传疾病的功能功能障碍。